Hippocampus-sensitive and striatum-sensitive learning one month after morphine or cocaine exposure in male rats

Abstract

These experiments examined whether exposure to drugs of abuse altered the balance between hippocampal and striatal memory systems as measured long after drug treatments. Male rats received injections of morphine (5 mg/kg), cocaine (20 mg/kg), or saline for five consecutive days. One month later, rats were then trained to find food on a hippocampus-sensitive place task or a striatum-sensitive response task. Relative to saline controls, morphine-treated rats exhibited impaired place learning but enhanced response learning; prior cocaine exposure did not significantly alter learning on either task. Another set of rats was trained on a dual-solution T-maze that can be solved with either place or response strategies. While a majority (67%) of control rats used place solutions in this task, morphine treatment one month prior resulted in a shift to response solutions exclusively (100%). Prior cocaine treatment did not significantly alter strategy selection. Molecular markers related to learning and drug abuse were measured in the hippocampus and striatum one month after drug exposure in behaviorally untested rats. Protein levels of glial-fibrillary acidic protein (GFAP), an intermediate filament specific to astrocytes, increased significantly in the hippocampus after morphine, but not after cocaine exposure. Exposure to morphine or cocaine did not significantly change levels of brain-derived neurotrophic factor (BDNF) or a downstream target of BDNF signaling, glycogen synthase kinase 3{beta} (GSK3{beta}), in the hippocampus or striatum. Thus, exposure to morphine results in a long-lasting shift from hippocampal toward striatal dominance during learning. The effects of prior morphine injections on GFAP suggest that long-lasting alterations in hippocampal astrocytes may be associated with these behavioral strategy shifts.